Possible role of the gut microbiome in mediating the beneficial effects of the six-herbal formulation STW 5-II on digestive health.

BACKGROUND: STW 5-II is a combination of six herbal extracts with clinically proven efficacy in functional dyspepsia (FD) and irritable bowel syndrome (IBS). STW 5-II contains a wide variety of secondary plant constituents that may interact with the human gut microbiome. In addition to complex carbohydrates, secondary plant metabolites, such as polyphenols, are known to exert prebiotic-like effects. PURPOSE: This study aimed to assess the bidirectional interactions between STW 5-II and the human gut microbiome. METHODS: STW 5-II was incubated with human fecal microbiota in a short-term colonic model. In the samples, the impact of STW 5-II on microbial fermentation capacity (pH, gas production), short chain fatty acid (SCFA) production, and microbial composition (Illumina 16S rRNA gene sequencing) was analyzed. In addition, the biotransformation of STW 5-II constituents by the fecal microbiota was assessed by UHPLCHRMS-based metabolite profiling. Furthermore, Caco-2/THP1 co-culture assay was used to explore the effect on gut barrier integrity and inflammatory markers. RESULTS: Fermentation of STW 5-II by fecal microbiota led to consistent changes in pH and gas production and increased production of SCFAs (acetate, propionate, and butyrate). STW 5-II promoted the enrichment of Bifidobacteriaceae, Lachnospiraceae, Ruminococcaceae, Erysipelotrichaceae, and Eggerthellaceae and suppressed the growth of pathogenic species from the Enterobacteriaceae family. In Caco2/THP1 culture, treatment with STW 5-II-incubated samples resulted in significantly increased transepithelial electrical resistance, indicating enhanced barrier function. Among inflammatory markers, STW 5-II-incubated samples increased LPS-induced secretion of the anti-inflammatory cytokine IL-10, as well as NF-κB activity, and significantly decreased the secretion of the pro-inflammatory chemokine MCP-1. UHPLCHRMS analysis identified 110 constituents of STW 5-II with changed levels during incubation with fecal microbiota: 63 constituents that were metabolized, 22 intermittently increased metabolites, and 25 final metabolites, including compounds with established anti-inflammatory activity, such as 18ß-glycyrrhetinic acid. CONCLUSION: These findings indicate a microbiome-mediated digestive health-promoting effect of STW 5-II via three different routes, namely enhanced microbial SCFA production, microbial production of potentially bioactive metabolites from STW 5-II constituents, and prebiotic-like action by promoting the proliferation/growth of beneficial bacteria.

Assessment of anti-inflammatory properties of extracts from Honeysuckle (Lonicera sp. L., Caprifoliaceae) by ATR-FTIR spectroscopy.

Inflammation is a hallmark of some of today's most life-threatening diseases such as arteriosclerosis, cancer, diabetes and Alzheimer's disease. Herbal medicines (HMs) are re-emerging resources in the fight against these conditions and for many of them, anti-inflammatory activity has been demonstrated. However, several aspects of HMs such as their multi-component character, natural variability and pharmacodynamic interactions (e.g. synergism) hamper identification of their bioactive constituents and thus the development of appropriate quality control (QC) workflows. In this study, we investigated the potential use of Attenuated Total Reflectance Fourier Transform Infrared (ATR-FTIR) spectroscopy as a tool to rapidly and non-destructively assess different anti-inflammatory properties of ethanolic extracts from various species of the Genus Lonicera (Caprifoliaceae). Reference measurements for multivariate calibration comprised in vitro bioactivity of crude extracts towards four key players of inflammation: Nitric oxide (NO), interleukin 8 (IL-8), peroxisome proliferator-activated receptor ß/δ (PPAR ß/δ), and nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB). Multivariate analysis of variance (MANOVA) revealed a statistically significant, quantitative pattern-activity relationship between the extracts' ATR-FTIR spectra and their ability to modulate these targets in the corresponding cell models. Ensemble orthogonal partial least squares (OPLS) discriminant models were established for the identification of extracts exhibiting high and low activity with respect to their potential to suppress NO and IL-8 production. Predictions made on an independent test set revealed good generalizability of the models with overall sensitivity and specificity of 80% and 100%, respectively. Partial least squares (PLS) regression models were successfully established to predict the extracts' ability to suppress NO production and NF-κB activity with root mean squared errors of cross-validation (RMSECV) of 8.7% and 0.05-fold activity, respectively.

Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor.

AIMS: To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41-2272, and activator, BAY 60-2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO). METHODS: Fifty-six male Sprague-Dawley rats were used, 31 of them underwent PUO. Fourteen rats were used for Western blots to assess PDE5 and sGC expression. For drug evaluation cystometry without anesthesia was performed three days following bladder catheterization. RESULTS: Obstructed rats showed higher micturition frequency and bladder pressures than non-obstructed animals (Intermicturition Interval, IMI, 2.28 ± 0.55 vs. 3.60 ± 0.60 min (± standard deviation, SD); maximum micturition pressure, MMP, 70.1 ± 8.0 vs. 48.8 ± 7.2 cmH2O; both P < 0.05). In obstructed rats vardenafil, BAY 41-2272, and BAY 60-2770 increased IMI (2.77 ± 1.12, 2.62 ± 0.52, and 3.22 ± 1.04 min; all P < 0.05) and decreased MMP (54.4 ± 2.8, 61.5 ± 11.3, and 51.2 ± 6.3 cmH2O; all P < 0.05). When vardenafil was given following BAY 41-2272 or BAY 60-2770 no further urodynamic effects were observed. PDE5 as well as sGC protein expression was reduced in obstructed bladder tissue. CONCLUSIONS: Targeting sGC via stimulators or activators, which increase the levels of cGMP independent of endogenous NO, is as effective as vardenafil to reduce urodynamic signs of BO. Targeting the NO/cGMP pathway via compounds acting on sGC might become a new approach to treat BO.

Phytochemical composition and in vitro pharmacological activity of two rose hip (Rosa canina L.) preparations.

The aim of the present study was to compare powdered rose hip with and without fruits (Rosae pseudofructus cum/sine fructibus, Rosa canina L., Rosaceae) with regard to their phytochemical profile and their in vitro anti-inflammatory and radical-scavenging properties. The two powders were subsequently extracted with solvents of increasing polarity and tested for inhibition of cyclooxygenase (COX-1, COX-2) and of 5-LOX-mediated leukotriene B(4) (LTB(4)) formation as well as for DPPH-radical-scavenging capacity. While the water and methanol extracts were inactive in the COX-1, COX-2 and LTB(4) inhibition assays, the n-hexane and the dichloromethane extracts inhibited all three enzymes. In the active extracts, the triterpenoic acids ursolic acid, oleanolic acid and betulinic acid were identified, although only in minute amounts. Furthermore, oleic, linoleic and alpha-linolenic acid were identified apart from several saturated fatty acids. Even though unsaturated fatty acids are known to be good inhibitors of COX-1, COX-2 and LT formation, no clear correlation between their concentration in the extracts and their activity was found. We suggest that other, yet unidentified, lipophilic constituents might play a more important role for the observed in vitro inhibitory activity on arachidonic acid metabolism. Some of the extracts also showed considerable DPPH radical scavenging activity, the methanolic extracts being most potent. The radical scavenging activity of the extracts correlated very well with their total phenolic content, while ascorbic acid contributes only little to the radical-scavenging activity due to its low concentration present in the extracts. In summary, extracts derived from powdered rose hip without fruits were more effective in all assays carried out compared with extracts derived from powdered rose hip with fruits.

Pharmacokinetics and immunomodulatory effects of phytotherapeutic lozenges (bonbons) with Echinacea purpurea extract.

The relative bioavailability of the major alkamides, dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides, from Echinacea purpurea phytotherapeutic lozenges at three different dose levels (0.07, 0.21 and 0.9 mg) was evaluated in a pharmacokinetic study in humans and the possible effects on the immunological system were measured. Alkamides were found to be rapidly absorbed and measurable in plasma 10 min after administration of 0.21 and 0.9 mg lozenges and remained detectable for 3h for the 0.21 mg lozenges and for more then 3h for the 0.9 mg lozenges; 0.07 mg lozenges were measurable 20 min after administration and remained detectable for only 2h after the administration. A significant dose-independent down-regulation of the pro-inflammatory cytokines IL-12p70, IL-8, IL-6, IL-10 and TNF was observed 24h after oral administration. The results of non-compartmental pharmacokinetic analysis revealed that a C(max) of (0.65+/-0.41 ng/ml) was reached at 32 min with the 0.07 mg lozenges, (1.00+/-0.21ng/ml) at 25 min with the 0.21 mg lozenges and (8.88+/-5.89 ng/ml) at 19 with the 0.9mg lozenges. As evidenced by the dose-exposure relationship, no significant departure from dose proportionality was observed, indicating linearity in pharmacokinetics. To get a further insight in pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides a compartmental population pharmacokinetic model was developed applying mixed effect modelling procedure. The results demonstrate that within the dose range studied pharmacokinetics of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamides are linear and that absorption is very rapid (t(1/2)=6 min) with apparently no lag time, thus indicating the possibility that a fraction of the drug is absorbed through the oral mucosa.

Immunologic analysis of monoclonal and immunoglobulin E antibody epitopes on natural and recombinant Amb a 1.

BACKGROUND: Amb a 1 is the major allergen from ragweed pollen and more than 90% of ragweed-allergic patients react with this protein. Although Amb a 1 was cloned and sequenced in 1991, little is known of the specificity of anti-Amb a 1 antibodies or of the immunologic properties of the recombinant allergen. OBJECTIVE: To compare binding of monoclonal antibodies (mAb) and IgE antibodies to purified natural Amb a 1 (nAmb a 1) and recombinant Amb a 1 (rAmb a 1). METHODS: Binding of a panel of anti-Amb a 1 mAb and IgE antibodies to nAmb a 1 or rAmb a 1 was compared by immunoblotting. Chimeric ELISA was used to measure specific IgE to these allergens using 89 ragweed-allergic sera from Austria, Italy, Canada and the United States. RESULTS: The 8 mAb bound to a 38 kDa Amb a 1 band in ragweed pollen extract and a subset of 5 mAb also bound to the 26 kDa chain of nAmb a 1. A two-site ELISA was developed using a mAb pair, which was approximately 10-fold more sensitive to rAmb a 1. There was a significant correlation between IgE antibody binding to nAmb a 1 and rAmb a 1 (n=89, r=0.79, P<0.001). A subset of approximately 40% of patients showed greater reactivity to nAmb a 1 than to rAmb a 1. CONCLUSIONS: The data suggest that there is less reactivity of human IgE to rAmb a 1 compared with nAmb a 1. The development of more sensitive, quantitative ELISA for Amb a 1 will require the production of new mAb especially directed against nAmb a 1.

[Conservative treatment of urinary incontinence]. / Was Sie konservativ anbieten können.

Urinary incontinence can be treated with medicinal products in addition to active pelvic floor muscle training and electrostimulation. A local hormone therapy should be first discussed with the gynaecologist. The active substance duloxetine has been used for a few years for treating stress incontinence. Several older and newer active substances are available for treating irritable bladder and stress incontinence.

Bioavailability and pharmacokinetics of Echinacea purpurea preparations and their interaction with the immune system.

Echinacea is a widely used herbal remedy for the prevention and treatment of the common cold. Recently, many new insights concerning the molecular mode of action of the main lipophilic constituents, the alkamides, have renewed interest in this plant. In order to compare the bioavailability of alkamides from liquid and tablet preparations of E. purpurea (Echinaforce) in humans and to study the effects on ex vivo stimulated blood cells, a randomized, single-dose, crossover study with 10 (8 test, 2 placebo) volunteers has been performed. They received either 4 ml of the standardized E. purpurea (Echinaforce) tincture or 12 E. purpurea (Echinaforce) tablets or placebo. Both doses contained the same amount (0.07 mg) of the major alkamides, dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides. Liquid chromatography electrospray ionization ion-trap mass spectrometry was used to determine the content of alkamides in serum. It was found that the arithmetic mean C(max) of dodeca-2E,4E, 8Z,10E/Z-tetraenoic acid isobutylamides absorbed after oral application of the Echinaforce tincture appeared after 30 min (0.40 ng/ml serum). In comparison, the t(max) of tablets was 45 min with a C(max) of 0.12 ng/ml. An ex vivo stimulation of blood by LPS was carried out to measure the influence of E. purpurea on the innate and adaptive immune system. Both E. purpurea preparations led to the same effects on the immune system according to the concentration of pro-inflammatory cytokines TNF-alpha and IL-8. 23 hours after oral application a significant down-regulation of TNF-alpha and IL-8 in LPS pre-stimulated whole blood was found. However, no significant changes in the concentration of IL-6 were observed. Although a quarter of the dodeca-2E,4E,8Z, 10E/Z-tetraenoic acid isobutylamides was absorbed from the tablets, the study shows that the formulations trigger the same effects on the measured immune parameters.

Knipholone, a selective inhibitor of leukotriene metabolism.

Inhibition of leukotriene formation is one of the approaches to the treatment of asthma and other inflammatory diseases. We have investigated knipholone, isolated from the roots of Kniphofia foliosa, Hochst (Asphodelaceae), for inhibition of leukotriene biosynthesis in an ex vivo bioassay using activated human neutrophile granulocytes. Moreover, activities on 12-lipoxygenase from human platelets and cycloxygenase (COX)-1 and -2 from sheep cotyledons and seminal vesicles, respectively, have been evaluated. Knipholone was found to be a selective inhibitor of leukotriene metabolism in a human blood assay with an IC(50) value of 4.2microM. However, at a concentration of 10microg/ml, the compound showed weak inhibition of 12(S)-HETE production in human platelets and at a concentration of 50microM it produced no inhibition of COX-1 and -2. In our attempt to explain the mechanism of inhibition, we examined the antioxidant activity of knipholone using various in vitro assay systems including free radical scavenging, non-enzymatic lipid peroxidation, and metal chelation. Knipholone was found to be a weak dose-independent free radical scavenger and lipid peroxidation inhibitor, but not a metal chelator. Therefore, the leukotriene biosynthesis inhibitory effect of knipholone was evident by its ability either to inhibit the 5-lipoxygenase activating protein (FLAP) or as a competitive (non-redox) inhibitor of the enzyme. Cytotoxicity results also provided evidence that knipholone exhibits less toxicity for a mammalian host cell.

Echinacea for preventing and treating the common cold.

BACKGROUND: Preparations of the plant Echinacea (family Compositae) are widely used in some European countries and in North America for common colds. Most consumers and physicians are not aware that products available under the term Echinacea differ appreciably in their composition, mainly due to the use of variable plant material, extraction methods and addition of other components. OBJECTIVES: The objective of this review was to assess whether there is evidence that Echinacea preparations are 1) more effective than no treatment; 2) more effective than placebo; 3) similarly effective to other treatments in A) the prevention and B) the treatment of the common cold. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005); PubMed (1997 to April 2005), EMBASE (1998 to June 2005), AMED (to August 2005), Centre for Complementary Medicine Research (in Munich) (1988 to May 2005), contacted experts, and screened references of reviews. SELECTION CRITERIA: We included randomized controlled trials that compared mono-preparations of Echinacea with a placebo, no treatment, or another treatment for the prevention or treatment of common colds. Trials on combinations of Echinacea and other herbs were excluded. DATA COLLECTION AND ANALYSIS: For all studies, at least two authors independently assessed eligibility and trial quality, and extracted data. Outcomes of interest in prevention trials were: numbers of individuals with one or more colds, and severity and duration of colds; and in treatment trials: total symptom scores, nasal symptoms, and duration of colds. MAIN RESULTS: Sixteen trials including a total of 22 comparisons of an Echinacea preparation and a control group (19 with placebo, 2 with no treatment, 1 with another herbal preparation) met the inclusion criteria. All trials except one were described as double-blind. The majority had reasonable to good methodological quality. Three comparisons investigated prevention of colds and 19 comparisons tested treatment of colds. A variety of different Echinacea preparations were used. None of the three comparisons in the prevention trials showed an effect over placebo. Comparing an Echinacea preparation with placebo as treatment, a significant effect was reported in nine comparisons, a trend in one, and no difference in six. More than one trial was available only for preparations based on the aerial parts from Echinacea purpurea (E. purpurea). AUTHORS' CONCLUSIONS: Echinacea preparations tested in clinical trials differ greatly. There is some evidence that preparations based on the aerial parts of Echinacea purpurea might be effective for the early treatment of colds in adults but results are not fully consistent. Beneficial effects of other Echinacea preparations, and for preventative purposes might exist but have not been shown in independently replicated, rigorous randomized trials.

Prostaglandin-H-synthase (PGHS)-1 and -2 microtiter assays for the testing of herbal drugs and in vitro inhibition of PGHS-isoenzyms by polyunsaturated fatty acids from Platycodi radix.

In order to test inhibition of prostaglandin-H-synthase-1 and -2 (PGHS-1 and -2) by plant extracts, we have established two enzyme based in vitro assays with enzyme immunoassay (EIA) evaluation. The assays have been evaluated with known synthetic inhibitors and with plant extracts. In a screening of traditionally used Chinese herbs for anti-inflammatory activity, a series of n-hexane and dichloromethane extracts showed significant inhibitory effect in comparison with the known specific PGHS-2 inhibitors NS-398 (IC(50) = 2.6 microM) and nimesulide (IC(50) = 36 microM). The lipophilic extracts of the Chinese drug Jiengeng, the dried roots of Platycodon grandiflorum (Jacq.) A. DC. (Campanulaceae), showed good inhibitory activity against both PGHS isoenzymes. The directly prepared DCM-extract exhibited better activity against PGHS-2 (IC(50) = 4.0 microg/ml) than against PGHS-1 (IC(50) = 17.6 microg/ml). We identified fatty acids as main active constituents and quantified them. Linoleic acid showed the highest content (ca. 20% of the dried extract) and a high and preferential PGHS-2 inhibitory activity (IC(50) (PGHS-1) = 20 microM; IC(50) (PGHS-2) = 2 microM). The comparison of the concentration of linoleic acid and the inhibitory activity of the direct DCM-extract showed, that linoleic acid is mainly responsible for the in vitro activity of the extract on PGHS-2.

A proprietary extract from the echinacea plant (Echinacea purpurea) enhances systemic immune response during a common cold.

In a previous paper, it was reported that Echinilin (Factors R & D Technologies, Burnaby, British Columbia, Canada) a formulation prepared from freshly harvested Echinacea purpurea plants and standardized on the basis of three known active components (alkamides, cichoric acid and polysaccharides) is effective for the treatment of a naturally acquired common cold. However, the mechanism by which this effect is achieved remains unknown. In the present study, Echinilin or placebo were administered to volunteers at the onset of their cold for a period of 7 days, with eight doses (5 mL/dose) on day 1 and three doses on subsequent days. Fasting blood samples were obtained before and during their colds. The decrease in total daily symptomatic score was more evident in the echinacea group than in the placebo group. These effects of echinacea were associated with a significant and sustained increase in the number of circulating total white blood cells, monocytes, neutrophils and NK cells. In the later part of the cold, the echinacea treatment suppressed the cold-related increase in superoxide production by the neutrophils. These results suggest that Echinilin, by enhancing the non-specific immune response and eliciting free radical scavenging properties, may have led to a faster resolution of the cold symptoms.

Are national quality standards for traditional Chinese herbal medicine sufficient? Current governmental regulations for traditional Chinese herbal medicine in certain Western countries and China as the Eastern origin country.

Traditional Chinese herbal Medicine (TCHM) has been gaining interest and acceptance world wide. TCHM provides on the one side promising perspective of scientific interest and on the other side possible health risks if TCHM drugs are not controlled with respect to quality standards or if practitioners for TCHM are not well trained. This paper outlines an introduction to the scientific aspects and potential risks of TCHM therapy followed by a brief, exploratory overview of the current status of TCHM regulations in certain Western countries like the USA, United Kingdom, Germany, Australia and in China as the Eastern origin country of TCHM. Legal foundations to establish quality and safety standards for TCHM crude drugs and ready-made formulas exist in some countries on a local basis but in practice are poorly enforced, where this products have no drug status. In addition practitioners treating patients with TCHM should be well versed in the pharmacology, side effects, and interactions of these substances with Western medicines and should be certified on a regular basis.

HPLC-coupled spectroscopic techniques (UV, MS, NMR) for the structure elucidation of phthalides in Ligusticum chuanxiong.

Ligusticum chuanxiong Hort., a plant that is frequently used in traditional Chinese medicine, has been studied using HPLC-coupled spectroscopic techniques such as HPLC-UV, HPLC-MS as well as HPLC-NMR. With the aid of these modern spectroscopic techniques, the main constituents, namely senkyunolide A, butylphthalide, neocnidilide and Z-ligustilide, have been characterized and identified. Phthalide dimers, present in smaller amounts, have been identified by HPLC-UV and HPLC-MS analysis and compared with reference compounds. Stereochemical features of some phthalide monomers have been determined by detailed spectroscopic studies for the first time.

Petasites hybridus extracts in vitro inhibit COX-2 and PGE2 release by direct interaction with the enzyme and by preventing p42/44 MAP kinase activation in rat primary microglial cells.

Rhizomes of butterbur, Petasites hybridus L. (Asteraceae), have been used since ancient times for the treatment of inflammatory diseases. In the present study, the effects of lipophilic extracts from rhizomes of Petasites hybridus on the formation and release of prostaglandin E2 were investigated. The extracts had different contents of petasin and isopetasin: A: 2.1 % and 0.4 %, B: 0.2 % and 0.1 %, C: 12.1 % and 6.1 % and D: 21.9 % and 9.4 %, respectively. Direct inhibition of cyclooxygenase (COX) -1 and -2 isoenzymes and inhibition of the expression of COX-2 and p42/44 MAP kinase in rat primary microglial cells were tested. All extracts were found to be only weak direct inhibitors of COX-1 (IC50> 400 microg/mL). However, most extracts revealed a strong inhibitory activity against the inducible isoform COX-2 ( A: IC50=30.4 microg/mL; B: IC50=60.6 microg/mL; C: IC50=22.6 microg/mL; D: IC50=20.0 microg/mL). This activity was not correlated to the content of petasin and isopetasin. Pure petasin and isopetasin neither inhibited COX-1 nor COX-2 (IC50 > 400 microM for both compounds and enzymes). Petasites extracts dose-dependently inhibited LPS-induced and thus COX-2-mediated PGE2 release in primary rat microglial cells (A: IC50= 2.4 microg/mL; C: IC50=5.8 microg/mL and D: IC50=4.6 microg/mL). Also this effect was independent from the petasin and isopetasin content. COX-2 synthesis in microglia was totally blocked with 5 microg/mL of C whereas COX-1 synthesis was not influenced. C and D did not affect the LPS-induced activation of p38 MAPK and IkappaBalpha, but they prevented the LPS-induced activation of p42/44 MAPK. Therefore, these Petasites hybridus extracts can be regarded as natural selective inhibitors of COX-2 and its expression, an effect which is independent from the petasin content.

Efficacy of a standardized echinacea preparation (Echinilin) for the treatment of the common cold: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Recently, echinacea has regained popularity as one of the treatments chosen most commonly by consumers with the expectation that it will reduce the severity and duration of the common cold. However, the results from a limited number of clinical trials for this application have thus far been inconclusive. This incongruity may be the result of investigators utilizing poorly standardized echinacea products, likely devoid of sufficient quantities of active constituents necessary to exert a definitive clinical effect. Therefore, a formulation containing alkamides, cichoric acid, and polysaccharides at concentrations of 0.25, 2.5, and 25 mg/mL, respectively, was prepared from freshly harvested Echinacea purpurea plants (commercially available as Echinilin, Natural Factors Nutritional Products, Inc., Vancouver, BC, Canada). The objective of this study was to test the efficacy of this highly standardized formulation in reducing the severity and duration of symptoms of a naturally acquired common cold. METHODS: In a randomized, double-blind, placebo-controlled trial, 282 subjects aged 18-65 years with a history of two or more colds in the previous year, but otherwise in good health, were recruited. The subjects were randomized to receive either echinacea or placebo. They were instructed to start the echinacea or placebo at the onset of the first symptom related to a cold, consuming 10 doses the first day and four doses per day on subsequent days for 7 days. Severity of symptoms (10-point scale: 0, minimum; 9, maximum) and dosing were recorded daily. A nurse examined the subjects on the mornings of days 3 and 8 of their cold. RESULTS: A total of 128 subjects contracted a common cold (59 echinacea, 69 placebo). The total daily symptom scores were found to be 23.1% lower in the echinacea group than in placebo in those who followed all elements of the study protocol (P<0.01). Throughout the treatment period, the response rate to treatments was greater in the echinacea group. A few adverse event profiles were observed in both groups. CONCLUSIONS: Early intervention with a standardized formulation of echinacea resulted in reduced symptom severity in subjects with naturally acquired upper respiratory tract infection. Further studies with larger patient populations appear to be warranted.

Effects of tenuiorin and methyl orsellinate from the lichen Peltigera leucophlebia on 5-/15-lipoxygenases and proliferation of malignant cell lines in vitro.

The orcinol derivatives tenuiorin (1) and methyl orsellinate (2) were identified as active components of an extract from the lichen Peltigera leucophlebia (Nyl.) Gyeln. showing in vitro inhibitory activity against 15-lipoxygenase from soybeans. The compounds were subsequently tested for in vitro activity against 5-lipoxygenase from porcine leucocytes and proved to be moderately active, with IC50 values of 41.6 microM and 59.6 microM respectively. Tenuiorin is a known constituent of several Peltigera species but has not previously been isolated from P. leucophlebia. As correlation between 5-lipoxygenase inhibition and antiproliferative effects has earlier been witnessed for related lichen metabolites, tenuiorin and methyl orsellinate were further tested for antiproliferative activity on cultured human breast (T-47D)-, pancreatic (PANC-1)- and colon (WIDR) cancer cell lines. The monomeric methyl orsellinate exhibited no detectable antiproliferative activity whereas the trimeric tenuiorin caused moderate/weak reduction in [3H]-thymidine uptake of the pancreatic- and colon cancer cells, with ED50 values of 87.9 and 98.3 microM respectively.

[New knowledge regarding the effect and effectiveness of Echinacea purpurea extracts]. / Neue Erkenntnisse zur Wirkung und Wirksamkeit von Echinacea purpurea-Presssaftzubereitungen.

Preparations made from the pressed juice of the flowering aerial parts of the Purple Coneflower, Echinacea purpurea (L.) Moench represent the most commonly used herbal immunnomodulatory agents. They are frequently administered for the supportive treatment of common viral infections of the upper respiratory tract. New clinical studies are reviewed, which demonstrated that corresponding preparations can diminish the severity and the length of common colds significantly, and that they can also be used efficiently for the treatment of children. New investigations have also shown, that stimulation of makrophages and induction of cytokins are major parts of the mode of action, and that glycoproteins/polysaccharides and alkamides are part of the activity relevant constituents.

Transport of alkamides from Echinacea species through Caco-2 monolayers.

To gain more insights into the human intestinal absorption of alkamides from Echinacea species, transport studies were performed with the human adenocarcinoma colonic cell line Caco-2 (ATCC) as a model to assess the epithelial transport of dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2). 30 minutes after apical loading of 25 microg/ml 1/ 2, about 15 % of these alkamides were detectable on the basolateral side. Close monitoring of the transport during 6 hours revealed a nearly complete transport to the basolateral side after 4 hours and no significant metabolism was observable. Transport experiments performed at 4 degrees C showed only a slight decrease in transport, which is a strong hint that dodeca-2 E,4 E,8 Z,10 E/ Z-tetraenoic acid isobutylamides (1/ 2) cross biological membranes by passive diffusion. Nearly the same results were obtained after preincubation of the Caco-2 cells with lipopolysaccharides (LPS) or phorbol 12-myristate-13-acetate (PMA) to mimic an inflammatory status. These results support the assumption that the alkamides can be easily transported from the intestinum and hence may contribute to the in vivo effects of Echinacea preparations.

Absorption of dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides after oral application of Echinacea purpurea tincture.

Alkamides are suspected to contribute to the activity of Echinacea preparations. In preliminary experiments a quantification method for dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides in human blood has been developed by which it was possible to detect dodeca-2E,4E,8Z,10E/Z-tetraenoic acid isobutylamides in human blood after oral application of Echinacea purpurea mother tincture.